Abstract: This proposal focuses on understanding the relationship between dietary patterns and risk of obesity in Hispanic women. This is an important issue in the realm of health disparities because neariy 80% of Hispanic women in the United States are ovenweight or obese and obesity increases risk for numerous chronic diseases, including breast cancer. The overall goal of this project Is to test the metabolic response to Western -and Indigenous Mexican diets in Hispanic women. We will also investigate whether ancestral genetic variation mediates the response to each diet. We hypothesize that the biological response to a Western dietary pattern produces detrimental metabolic profiles favoring adipose deposition, which leads to increased risk of adverse health events, including increased risk of breast cancer. Conversely, we hypothesize that the physiologic response to an Indigenous Mexican diet will produce a favorable metabolic profile. We further hypothesize that genetic ancestry mediates this biological response to a Western dietary pattern. Our primary aims are: (1) To test in a randomized cross-over experimental feeding study the metabolic response to an Indigenous Mexican diet vs. a Western diet in 50 first and second generation Hispanic women living in the greater Seattle area. The metabolic response will be measured by blood concentrations ofthe following biomarkers assessed before and after each feeding period: insulin, glucose, IGFI, IGFBP3, leptin, adiponectin, IL-6, CRP and SAA;and (2) To investigate whether genetic characteristics, as assessed with Ancestry Informative Markers, mediate the metabolic response to each tested diet. As secondary alms we will examine measures of hunger and satiety during each diet test period and genetic predictors of adiposity. This project will provide important data for understanding the etiology of obesity in i-lispanic women, which can be used to design effective programs for prevention.